Apoptotic β-cells induce macrophage reprogramming under diabetic conditions.

ABSTRACT: Type 2 diabetes mellitus (T2DM) occurs when insulin-producing pancreatic β-cells fail to secrete sufficient insulin to compensate for insulin resistance. As T2DM progresses, apoptotic β-cells need to be removed by macrophages through efferocytosis that is anti-inflammatory by nature. Paradoxically, infiltrating macrophages are a main source of inflammatory cytokines that leads to T2DM. It is unclear how apoptotic β-cells impact macrophage function. We show under diabetic conditions, phagocytosis of apoptotic β-cells causes lysosomal permeabilization and generates reactive oxygen species that lead to inflammasome activation and cytokine secretion in macrophages. Efferocytosis-induced lipid accumulation transforms islet macrophages into foam cell-like outside the context of atherosclerosis.

SUBMITTER: Ward MG 

PROVIDER: S-EPMC6200952 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature